Frequency and spectrum of ROS1 resistance mutations in ROS1-positive lung cancer patients progressing on crizotinib.

Abstract

9072Background: ROS1 rearrangements define a distinct molecular subset of non-small cell lung cancer (NSCLC) and confer sensitivity to treatment with the ALK/ROS1/MET inhibitor crizotinib. Despite the initial activity of this agent, ROS1-positive cancers ultimately develop resistance to therapy. To evaluate mechanisms of resistance to crizotinib among ROS1-positive patients, we examined a series of repeat biopsies from ROS1-positive patients progressing on crizotinib. Methods: Medical records were reviewed and data extracted. Repeat biopsies were performed as part of routine clinical care or under institutional review board (IRB)-approved protocols. Specimens underwent Sanger-based sequencing of the ROS1 kinase domain or targeted next-generation sequencing (NGS). Results: We identified 10 ROS1-positive patients who underwent repeat biopsies following acquired resistance to crizotinib. One patient underwent resection of 2 separate central nervous system (CNS) metastases. The most common sites of tissue col...